The overall objective of the proposed studies is an analysis of the influence of a number of factors upon the interaction between estradiol and its tissue receptors, and the subsequent biological activity arising therefrom. The approach is unique in that it is focused primarily upon low-affinity interactions which are uniformly ignored or overshadowed in most studies of receptor binding. One facet of the studies involves experimental manipulation of endogenous levels of thyroid hormones, and subsequent analysis of estrogen- receptor binding. Correlation will be made with gonadotropin release in an attempt to define the role of the thyroid in ovulation. A second aim of this work is to investigate the effects of a series of estrogens, anti-estrogens, androgens and progesterone upon the association rate of estradiol-receptor complex formation. Finally, receptor synthesis will be assessed in several estrogen-responsive tissues as a function of various administered hormones, including estradiol. All the work proposed herein is designed to afford a clearer understanding of the control of receptor populations, and consequently, the control of physiological responses to estrogens.